Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development,homeostasis,and disease of human intervertebral disks(IVDs)remains challenging.Here,the transcriptomic landscape of 108108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs,including the nucleus pulposus(NP),annulus fibrosus,and cartilage endplate(CEP).The chondrocyte subclusters were classified based on their potential regulatory,homeostatic,and effector functions in extracellular matrix(ECM)homeostasis.Notably,in the NP,a PROCR+resident progenitor population showed enriched colony-forming unit-fibroblast(CFU-F)activity and trilineage differentiation capacity.Finally,intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-βcascades are important cues in the NP microenvironment.In conclusion,a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.

Nerve regeneration following implantation of axotomized nerves pretreated with gamma radiation

BACKGROUND： It has been shown that irradiation to the neurolemma can reduce immuuogenicity. However, it is still poorly understood whether the degenerated nerve can affect peripheral nerve regeneration OBJECTIVE： To observe the effect of radiation-damaged nerve transplantation on functional recovery of the peripheral nerve. DESIGN, TIME AND SETTING： Self-control animal trial was performed at the Experimental Center of Orthopedics, Tangdu Hospital of Fourth Military Medical University from January to October 2005. MATERIALS： Fifty-four healthy, Chinese rabbits, irrespective of gender, were randomly divided into experimental （n = 36） and control （n = 18） groups. A 60 Co Y -radiation machine and NDI-200 nerve electromyograph were provided by the Experimental Center of Orthopedics, Tangdu Hospital of Fourth Military Medical University. METHODS： A median incision was made in the posterior right thigh of rabbits after abdominal anesthesia. A 30-mm segment of sciatic nerve was excised from the inferior margin of the piriform muscle to the tibiofibular intersection. The sciatic nerve in the experimental group was sterilely radiated with 350 Gy for 9.5 minutes. The damaged nerve segment was then re-transplanted. In the control group, the sciatic nerve was re-transplanted directly following excision. Nerve conduction velocity was determined at 4, 6, and 8 months post-surgery. MAIN OUTCOME MEASURES： Functional assessments, such as gait, nutritional status of skin on dorsum of foot, toe spreading reflex, and foot holding, were made between 1 and 180 days post-surgery. The common peroneal nerve and tibial nerve reflexes under clamping were observed at 4, 6, and 8 months post-surgery to evaluate functional restoration of the peripheral nerve. Electromyogram was performed to observe nerve conduction velocity. RESULTS： From postoperative days 1 to 26, the limbs that were transplanted with irradiated nerve exhibited dragged walking, foot drop, sole ulcers, depilation, self-induced injury to the toes, and other denervation behaviors. From 95 to 120 days after re-transplantation, the ulcers recovered, in addition to recovered toe-spreading reflex. When subjected to the clamping text, nerve reflex occurred. Compared with animals transplanted with normal nerve, nerve conduction velocity in the experimental group was slower at 4 and 6 months post-surgery （P 〈 0.05 and P 〈 0.01）. At 8 months after surgery, nerve conduction velocity recovered in the experimental group, but was still slower than the control group （P 〈 0.05）. Recovered conduction velocity in the experimental group was significantly faster than the control group （P 〈 0.05）. CONCLUSION： Reinnervation was achieved by pre-treating a 30-mm segment of sciatic nerve with 350-Gy radiation. Although radiation improved nerve conduction velocity recovery following re-transplantation, the velocity was not completely recovered to normal levels.

Calcar-guided short-stem total hip arthroplasty: Will it be the future standard? Review and perspectives

Short stems in total hip arthroplasty(THA)are becoming increasingly popular.In Germany,already 10.4%of all primary THAs are performed using a cementless short stem.The concept of modern,calcar-guided,short stems aims for an individualized reconstruction of the hip anatomy by following the calcar of the femoral neck,a bone-and soft-tissue-sparing implantation technique,and physiological loading.The stem design uses either metaphyseal fixation alone or additional diaphyseal anchoring,depending on the stem alignment and indication.These individualized anchorage types increase the potential indications for the safe use of a short stem.The design features may account for potential advantages of current short stem implants compared with earlier shortstem designs,particularly in cases of reduced bone quality or osteonecrosis of the femoral head and femoral neck fractures.The implantation technique,however,requires distinct knowledge regarding the characteristics of varus and valgus positioning,with the potential for clinical consequences.A learning curve for surgeons new to this technique must be taken into account.Cortical contact with the distal lateral cortex appears to be crucial to provide sufficient primary stability,and the use of intraoperative imaging to identify“undersizing”is highly recommended.Current results of several national registries indicate that calcarguided short stems are among the most successful implants in terms of mid-term survivorship.However,long-term data remain scarce.This review introduces the characteristics of calcar-guided short-stem THA and summarizes the current evidence.

A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn-1Mg porous scaffolds as biodegradable bone implants

Zinc(Zn)alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions,having a great application potential for repairing bone defect.In this work,a hydroxyapatite(HA)/polydopamine(PDA)composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion,and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin.The microstructure,degradation behavior,biocompatibility,antibacterial performance and osteogenic activities were systematically investigated.Compared with as-built Zn-1Mg scaffolds,the rapid increase of Zn2+,which resulted to the deteriorated cell viability and osteogenic differentiation,was inhibited due to the physical barrier of the composite coating.In vitro cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance.Significantly improved osteogenic and antibacterial functions were also observed according to in vivo implantation in the lateral femoral condyle of rats.The design,influence and mechanism of the composite coating were discussed accordingly.It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.

Clinical observation of acupuncture combined with sitting-position knee-adjustment manipulations for patellofemoral arthritis

Objective To observe the efficacy of acupuncture combined with sitting-position knee-adjustment manipulations in treating patellofemoral osteoarthritis.Methods Ninety-two patients with patellofemoral osteoarthritis were randomized into an observation group and a medication group,with 46 cases in each group.The observation group received acupuncture and sitting-position knee-adjustment manipulations,and the medication group received oral celecoxib capsules.After 8-week treatment,changes in the short-form McGill pain questionnaire(SF-MPQ)and Lysholm knee scoring scale(LKSS)scores were observed,and the clinical efficacy was compared.Results The total effective rate was 87.0%in the observation group and 63.0%in the control group;the between-group difference was statistically significant.Before treatment,there were no significant differences in the SF-MPQ score or LKSS score(P>0.05).After 8-week treatment,the SF-MPQ[including pain rating index(PRI),visual analog scale(VAS),and present pain intensity(PPI)]and LKSS scores showed notable changes in both groups(P<0.05);the SF-MPQ and LKSS scores in the observation group were significantly different from those in the control group(P<0.05).Conclusion Combining acupuncture and sitting-position knee-adjustment manipulations can reduce pain and ameliorate joint function in patients with patellofemoral osteoarthritis,producing more significant efficacy than oral celecoxib capsules.

Long-term clinical outcomes following total knee arthroplasty in patients with hemophilic arthropathy:a single-surgeon cohort after a 10-to 17-year follow-up

Background:Total knee arthroplasty(TKA)can reduce severe joint pain and improve functional disability in hemophilia.However,the long-term outcomes have rarely been reported in China.Therefore,this study aimed to evaluate the long-term outcomes and complications of TKA in Chinese patients with hemophilic arthropathy.Methods:We retrospectively reviewed patients with hemophilia who underwent TKA between 2003 and 2020,with at least 10 years of follow-up.The clinical results,patellar scores,patients’overall satisfaction ratings,and radiological findings were evaluated.Revision surgery for implants during the follow-up period was recorded.Results:Twenty-six patients with 36 TKAs were successfully followed up for an average of 12.4 years.Their Hospital for Special Surgery Knee Score improved from an average of 45.8 to 85.9.The average flexion contracture statistically significantly decreased from 18.1°to 4.2°.The range of motion(ROM)improved from 60.6°to 84.8°.All the patients accepted patelloplasty,and the patients’patellar score improved from 7.8 preoperatively to 24.9 at the last follow-up.There was no statistically significant difference in clinical outcomes between the unilateral and bilateral procedures,except for a better ROM at follow-up in the unilateral group.Mild and enduring anterior knee pain was reported in seven knees(19%).The annual bleeding event was 2.7 times/year at the last follow-up.A total of 25 patients with 35 TKAs were satisfied with the procedure(97%).Revision surgery was performed in seven knees,with 10-and 15-year prosthesis survival rates of 85.8%and 75.7%,respectively.Conclusions:TKA is an effective procedure for patients with end-stage hemophilic arthropathy,which relieves pain,improves knee functions,decreases flexion contracture,and provides a high rate of satisfaction after more than ten years of follow-up.

Superior biocompatibility and comparable osteoinductive properties: Sodium-reduced fluoride-containing bioactive glass belonging to the CaO–MgO–SiO2 system as a promising alternative to 45S5 bioactive glass

Bioactive glasses(BGs)are promising bone substitute materials.However,under certain circumstances BGs such as the well-known 45S5 Bioglass®(composition in wt%:45.0 SiO2,24.5 Na2O,24.5 CaO,6.0 P2O5)act cytotoxic due to a strong increase in pH caused by a burst release of sodium ions.A potential alternative is a sodiumreduced fluoride-containing BG belonging to the CaO–MgO–SiO2 system,namely BG1d-BG(composition in wt%:46.1 SiO2,28.7 CaO,8.8 MgO,6.2 P2O5,5.7 CaF2,4.5 Na2O),that has already been evaluated in-vitro,in-vivo and in preliminary clinical trials.Before further application,however,BG1d-BG should be compared to the benchmark amongst BGs,the 45S5 Bioglass®composition,to classify its effect on cell viability,proliferation and osteogenic differentiation of human mesenchymal stem cells(MSCs).Therefore,in this study,the biocompatibility and osteogenic potential of both BGs were investigated in an indirect and direct culture setting to assess the effect of the ionic dissolution products and the BGs’physical presence on the cells.The results indicated an advantage of BG1d-BG over 45S5 Bioglass®regarding cell viability and proliferation.Both BGs induced an earlier onset of osteogenic differentiation and accelerated the expression of late osteoblast marker genes compared to the control group.In conclusion,BG1d-BG is an attractive candidate for further experimental investigation.The basic mechanisms behind the different impact on cell behavior should be assessed in further detail,e.g.by further alteration of the BG compositions.

Wound healing in postbariatric body contouring surgery

Due to the continuous development in the field of bariatric surgery, there is an increasing need for postbariatric body contouring surgery. The morbidity of postbariatric patients predisposes them to develop wound healing complications. In this article we describe the preoperative, intraoperative and surgical factors influencing the wound healing and therefore the final outcome. The most common postbariatric body contouring procedures, including brachioplasty, breast contouring surgery, abdominoplasty/circumferential body lift and medial thigh lift are being discussed in terms of wound healing characteristics and subsequent complications. The preoperative preparing as well as special operative techniques are described in order to achieve a low rate of wound healing complications.